Metastatic Pancreatic Cancer
Conditions
Brief summary
This is a single arm, open label Phase II clinical trial to evaluate the efficacy and safety of donafenib combined with S-1 in treating Patients with metastatic pancreatic cancer after chemotherapy with Nab-paclitaxel plus gemcitabine regimen.
Detailed description
While NG ( Nab-paclitaxel + gemcitabine) is one of the preferred first-line chemotherapy for metastatic pancreatic cancer, we have to investigate possible therapeutic options after NG regimen. In this single arm, open-label clinical trial, metastatic pancreatic cancer patients will be received donafenib and S-1. Treatment repeats every 3 weeks until the disease recurrence or unacceptable toxicity, death or begin a novel therapeutic. The efficacy and safety data will be assessed through OS, ORR, DCR, PFS,TTP and adverse effects as graded by NCI CTC-AE 5.0.
Interventions
DRUGDonafenib
Donafenib: 200mg po bid.
DRUGS1
S-1 capsule: According to the body surface area \<1.25m2 40mg/d, 1.25 \ 1.5 m2 50 mg/d, \> 1.5m2 60mg/d po bid, taking 14 days, stopping for 7 days, 21 days for 1 cycle.
Sponsors
Fudan University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Informed consent and willing to complete the study according to the protocol. * Age ≥ 18 years and ≤ 75 years, and there is no limit on the gender * ECOG performance scale 0-1; * Diagnosed as pancreatic adenocarcinoma by histology and cytology; * Treatment of patients with advanced metastatic pancreatic cancer who have failed with NG (Nab-paclitaxel + gemcitabine) regimen(The disease progresses during the course of treatment or within 6 months after the end of treatment, with clear imaging evidence; this does not include patients with intolerable toxicity)； * Baseline blood routine and biochemical indexes meet the following criteria: 1. Blood routine examination criteria must be met: (no blood transfusion within 14 days) 1. HB≥90g/L； 2. ANC≥1.5×109/L； 3. PLT≥100×109/L. 2. Biochemical tests are subject to the following criteria: 1. BIL \<1.25xULN ； 2. ALT and AST\<2.5ULN； 3. Serum creatinine. Less than 1.5 times the upper limit of normal value, Endogenous creatinine clearance\>60ml/min ( Cockcroft-Gault formula). 4. Albumin≥28g/L. 3. Blood coagulation indexes are subject to the following criteria: 1. Prothrombin time (PT) and international normalized ratio (INR) ≤1.5 × ULN; 2. Activated partial thromboplastin time（APTT）≤1.5 × ULN. * According to the standard of RECIST 1.1, there is at least one imaging measurable lesion; * Life expectancy ≥ 3 months; * Patients and their families were willing to cooperate with follow-up.
Exclusion criteria
* Diagnosis of malignant diseases other than pancreatic cancer within 5 years prior to first administration (excluding cured skin basal cell carcinoma, squamous carcinoma of the skin, and/or resected carcinoma in situ); * Medical conditions that affect absorption, distribution, metabolism, or clearance of the study drug (e.g., severe vomiting, chronic diarrhea, intestinal obstruction, absorption disorders, etc.); * Patients with brain metastases or pial metastases; * Patients with a clear past history of neurological or psychiatric disorders, including epilepsy or dementia; * Comorbidities (e.g., severe or uncontrolled hypertension, severe diabetes, and/or thyroid disease) that, in the investigator's judgment, seriously endanger patients' safety or prevent them from completing the study; * The patient was currently participating in an interventional clinical study or had been treated with another study drug or study device in the 4 weeks prior to initial dosing; * The patient had a history of organ transplantation; * Concurrent administration of drugs that may prolong QTc and/or induce Tdp; * Patients also take drugs that affect drug metabolism; * HIV infection or acute or chronic viral hepatitis (hbSAG positive, HBV-DNA load ≥500IU/ml and/or HCV antibody positive); * Excluded patients with serious cardiovascular disease, including grade ≥II cardiac dysfunction (NYHA criteria); * Patients with severe gastrointestinal dysfunction (bleeding, infection, obstruction, or diarrhea greater than grade 1) were excluded; * Patients with abnormal coagulation function, bleeding tendency, or receiving thrombolytic or anticoagulant therapy were excluded; * Patients with a severe arterial thromboembolism event within 6 months were excluded; * Excluding women who are pregnant or breast-feeding.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | through study completion, an average of 1 year | To evaluate the overall survival of patients with advanced metastatic pancreatic cancer who have failed with NG (Nab-paclitaxel + gemcitabine) regimen after treatment with Donafenib combined with S-1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival | through study completion, an average of 1 year | To investigate the progression-free survival (PFS) of patients with advanced metastatic pancreatic cancer who have failed with NG (Nab-paclitaxel + gemcitabine) regimen after treatment with Donafenib combined with S-1. |
| Overall Response Rate | through study completion, an average of 1 year | To evaluate the overall response rate of patients with advanced metastatic pancreatic cancer who have failed with NG (Nab-paclitaxel + gemcitabine) regimen after treatment with Donafenib combined with S-1. |
| Incidence of Adverse Events | through study completion, an average of 1 year | Adverse events of patients with advanced metastatic pancreatic cancer who have failed with NG (Nab-paclitaxel + gemcitabine) regimen after treatment with Donafenib plus S-1. |
Countries
China
Outcome results
None listed